Evaluation of importance of polymorphisms in quinone oxidoreductases and superoxide dismutases for prediction of breast cancer risk and progression

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Background: NADP(H) quinone oxidoreductases (NQO1, OMIM no.: 125860 and NQO2, 160998) are flavoproteins performing two-electron reduction of quinoid compounds to hydroquinones thus preventing accumulation of reactive superoxide anionradical which is formed during spontaneous conversions of quinoids. Superoxide dismutases (SOD2, 147460 and SOD3, 185490) protect the cell against damage caused by excess of superoxide anion radical by its conversion to hydrogen peroxide. The aim of this study was to evaluate the importance of polymorphisms and haplotypes in NQO1, NQO2, SOD2 and SOD3 for development, progression and therapy outcome of breast cancer.
 >Materials and Methods: PCR with restriction fragment analysis was used to determine the frequency of polymorphisms in NQO1 (Pro187Ser, rs1800566)and NQO2 (Phe47Leu, rs1143684). Polymorphisms in SOD2 (Ala16Val, rs4880) and SOD3 (Arg231Gly, rs1799895) were determined by real-time PCR using TaqMan assays. Case-control study consisted of 300 breast cancer patients and 300 controls.
 >Results: Differences in distribution of genotypes and alleles between cases and controls, prevalence of two- and three- gene combinations and associations of polymorphisms with clinical and pathological data were analyzed by standard statistical approaches. Polymorphisms in NQO1, SOD2 and SOD3 did not associate with either risk or characteristics of breast cancer. Inheritance of variant Leu allele in NQO2 weakly decreased the risk of breast cancer (OR=0.68, 95%CI=0.46-1.01, p=0.053). Similarly, patients carrying this allele had significantly less often stage II-IV than regionally advanced stage I disease (OR=0.49, 95%CI=0.26-0.91, p=0.024). Combinations of polymorphisms did not significantly modify risk or progression of breast cancer. Comparison with therapy outcome and survival in long-term prospective is in progress.
 >Conclusions: The studied polymorphisms in NQO1, SOD2 and SOD3 and their combination do not seem to modify breast cancer risk and progression in Czech population. The importance of rs1143684 polymorphism in NQO2 should be clarified by larger study.
 >This study was supported by grant from the Grant Agency of Charles University, no.: 94507 and by Young Researcher Award from National Institute of Public Health.